Benoit Danielle S W, Anseth Kristi S
Department of Chemical and Biological Engineering, University of Colorado, Boulder, 80309-0424, USA.
Acta Biomater. 2005 Jul;1(4):461-70. doi: 10.1016/j.actbio.2005.03.002. Epub 2005 Apr 26.
Heparin was modified with methacrylate groups, copolymerized with dimethacrylated poly(ethylene glycol), and analyzed as a localized delivery vehicle for bFGF and synthetic extracellular matrix for the differentiation of hMSCs. By deriving cues from molecules normally present in the extracellular matrix (ECM), a complex network of collagens, laminin, fibronectin, glycosaminoglycans, and growth factors, synthetic cell scaffolds can be designed that actively sequester important bioactive signals. Among the glycosaminoglycans, heparin binds reversibly with many proteins, therefore, poly(ethylene glycol) based biomaterials, normally resistant to cell adhesion, functionalized with heparin in order to sequester important proteins, can actively and selectively stimulate desired cell functions. Results demonstrate that methacrylate-modified heparin retained its ability to bind heparin-binding proteins both in solution and when copolymerized with dimethacrylated PEG in a hydrogel. In addition, the heparin functionalized gels can deliver biologically active bFGF for up to 5 weeks. Finally, the gels were examined as a potential scaffold for hMSC culture and were found to promote adhesion, proliferation, and osteogenic differentiation.
肝素用甲基丙烯酸酯基团进行修饰,与二甲基丙烯酸化聚乙二醇共聚,并作为碱性成纤维细胞生长因子(bFGF)的局部递送载体和用于人间充质干细胞(hMSCs)分化的合成细胞外基质进行分析。通过从细胞外基质(ECM)中通常存在的分子获取线索,即由胶原蛋白、层粘连蛋白、纤连蛋白、糖胺聚糖和生长因子组成的复杂网络,可以设计出能主动隔离重要生物活性信号的合成细胞支架。在糖胺聚糖中,肝素能与许多蛋白质可逆结合,因此,通常对细胞黏附具有抗性的基于聚乙二醇的生物材料,经肝素功能化以隔离重要蛋白质后,可主动且选择性地刺激所需的细胞功能。结果表明,甲基丙烯酸酯修饰的肝素在溶液中以及与二甲基丙烯酸化聚乙二醇在水凝胶中共聚时,均保留了其结合肝素结合蛋白的能力。此外,肝素功能化凝胶可递送生物活性bFGF长达5周。最后,对该凝胶作为hMSC培养的潜在支架进行了检测,发现其能促进细胞黏附、增殖和成骨分化。